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KMID : 0620920090410060406
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Experimental & Molecular Medicine
2009 Volume.41 No. 6 p.406 ~ p.416
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Sterol-independent repression of low density lipoprotein receptor promoter by peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α)
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Jeong Jae-Hoon
Cho Se-Hyung
Kim Pak Young-Mi
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Abstract
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Peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) may be implicated in cholesterol metabolism since PGC-1α co-activates estrogen receptor α (ERα) transactivity and estrogen/ERα induces the transcription of LDL receptor (LDLR). Here, we show that overexpression of PGC-1α in HepG2 cells represses the gene expression of LDLR and does not affect the ERα-induced LDLR expression. PGC-1α suppressed the LDLR promoter-luciferase (pLR1563- luc) activity regardless of cholesterol or functional sterol-regulatory element-1. Serial deletions of the LDLR promoter revealed that the inhibition by PGC-1α required the LDLR promoter regions between -650 bp and -974 bp. Phosphorylation of PGC-1α may not affect the suppression of LDLR expression because treatment of SB202190, a p38 MAP kinase inhibitor, did not reverse the LDLR down-regulation by PGC-1α. This may be the first report showing the repressive function of PGC-1α on gene expression. PGC-1α might be a novel modulator of LDLR gene expression in a sterol-independent manner, and implicated in atherogenesis.
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KEYWORD
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cholesterol, liver, peroxisome-proliferator-tor-activated receptor-γ coactivator-1, PPARγ, promoter regions, genetic
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